A single layer of epithelial cells that actively self-renews and is organized into crypts and villi clothes the intestine. It has been recently shown that the renewal of intestinal epithelium is driven by Lgr5+ intestinal stem cells (ISC) that reside at the base of these crypts (Barker et al., 2007). Lgr5+ stem cells can be isolated and cultured in vitro to form organoids containing crypt-villus structures that recapitulates the native intestinal epithelium (Sato et al., 2009). While these stem cells can be expanded for multiple passages in the form of organoids, existing culture conditions provide little to no control over self-renewal and differentiation. Typical cultures consist of heterogeneous cell populations, including stem cells and differentiated cells (Sato et al., 2009). In particular, the self-renewal and proliferation of Lgr5+ stem cells both in vitro and in vivo are dependent on direct cell contact between Lgr5+ stem cells and another crypt cell type known as paneth cells (Snippert et al., 2010), which significantly complicates and limits the ability to control the fate of Lgr5+ stem cells in culture. The inability to efficiently expand Lgr5+ stem cells considerably limits the translation of this biology to therapies, where homogeneous stem cell cultures and efficient scale-up processes are essential prior to transplantation. Moreover, there remains a need to develop improved, clinically-oriented systems for transplantation of ex vivo expanded epithelial tissue into injured recipient organs.